Incorporation of 2nd and 3rd Generation Bisphosphonates on Hydroxyfluorapatite

Abstract

Bisphosphonates (BPs) may play an important role in minimizing osteolysis. In this work two new bisphosphonates pertaining to second and third generations respectively, have been synthesized and incorporated onto a chemically enriched hydroxyapatite. BP synthesis has been performed by adding H3PO3, PCl3 and methanesulfonic acid over 4-aminophenyl acetic acid (APBP) and 1-H-indole-3-acetic acid (IBP) respectively at 65°C in a N2 atmosphere. These
compounds bear a primary amine group bonded to an aromatic ring, and a secondary amine group within a heterocyclic ring respectively. A chemically enriched hydroxyapatite with a chemical content corresponding to a 50% fluorided hydroxyapatite has been synthesized. Ceramic bodies manufactured by uniaxial pressure followed by cold isostatic press have a 97% density and
submicron grain size. The BP was adsorbed onto the surface by immersion in a stirred solution at 37°C for 48 hours. A 10-fold decrease of the surface energy was observed for bodies modified with the APBP whereas only a 25 % decrease is obtained for bodies loaded with the bisphosphonate loaded with the IBP.